Phase II trial of ifosfamide and mesna in advanced ovarian carcinoma: a Gynecologic Oncology Group Study.

Abstract

Ifosfamide (isophosphamide) and mesna (2-mercaptoethane sodium sulfonate) were administered intravenously at monthly intervals to 46 patients with advanced epithelial ovarian carcinoma refractory to or recurrent after cisplatin-containing combination chemotherapy. Initially, ifosfamide was given as 1.5 g/m2/d x 5 days and mesna as 300 mg/m2 every 4 hours for three doses following ifosfamide, but the initial dose of ifosfamide was reduced to 1.2 g/m2 because of toxicity. Four of the patients initially entered were found to be ineligible: two who had had more than one prior chemotherapy regimen and two who did not have ovarian primaries. One patient received an inadequate trial and four patients had discontinuation of therapy because of toxicity, leaving 41 evaluable for response. Three patients (7.0%) had complete responses and five (13.0%) had partial responses for an overall response rate of 20.0%. Response duration ranged from 2.1 to 20.3 + months with a median of 6.9 + months. Two patients died of renal failure, one of whom had no known renal disease and received 1.5 g/m2/d x 5 days ifosfamide. The second patient received the 1.2 g/m2 dose and was found to have chronic pyelonephritis and pyonephrosis at autopsy. Gynecologic Oncology Group (GOG) grade 3 or 4 granulocytopenia was seen in eight (19.5%), grade 3 or 4 thrombocytopenia in four (9.8%), and grade 3 or 4 neurotoxicity in six (14.6%) of the 41 patients evaluable for toxicity. Ifosfamide/mesna is active in epithelial ovarian cancer. GOG trials in untreated patients are being initiated and toxicity is being evaluated.